The overall objectives of our studies are to come to a better understanding of the factors which regulate or modulate dopamine synthesis and release in the central nervous system (CNS). Major efforts are being directed toward elucidating the importance of autoreceptors in such regulation and modulation. Autoreceptors appear to be present on dopamine neurons in the CNS in an analogous fashion to alpha adrenoceptors on peripheral noradrenergic neurons. We are determining if such autoreceptors share similar pharmacological properties in different anatomical parts of the CNA. Moreover we are determining if receptors which mediate postsynaptic responses to dopamine have similar pharmacological characteristics as dopamine autoreceptors. We are also determining if autoreceptors or functions served by these receptors undergo changes in sensitivity following procedures which alter nerve activity. Finally, we are studying the interaction of opioid drugs (such as the enkephalins and morphine) which act synergistically or antagonistically with dopamine autoreceptors in altering dopamine synthesis and release.